This is a six center, double-blind, placebo-controlled study to determine if the administration of oral doxycycline will decrease the severity or progression of osteoarthritis (OA) in females. This is a 30 month clinical trial. Because the pathologic changes of OA progress slowly, obese women between ages of 45-64 with radiographic evidence of unilateral knee OA will be used as subjects. Our primary outcome measure will be radiographic OA progression in the contralateral knee.